# INDUCIBLE ANTIBIOTIC RESISTANCE

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 1992 · $116,533

## Abstract

The long-term general objective of this research program is to study
regulation of genes whose expression is induced or modified by antibiotics.
The emphasis is on a group of genes that confer antibiotic resistance.  The
specific aims of this proposal are to study regulation of
erythromycin-inducible resistance to the macrolide, lincosamide, and
streptogramin B (MLS) antibiotics conferred by Staphylococcus aureus
plasmid pEl94.  An inducible 23S rRNA methylase confers resistance by
methylating a specific adenine residue in 23S rRNA, and its synthesis is
induced by erythromycin.  Factors that enter into the control of MLS
resistance can be classified according to whether they act on: (1) the rate
of synthesis of the message (transcriptional control), (2) the rate of
degradation of the message (mRNA stability), (3) the efficiency of
utilization of the message (translational control), and (4) the number of
plasmid DNA copies that are available from which to transcribe the message
(plasmid copy number control).  Two new aspects of the problem that will
serve as the focus of the present work include: (1) a study of the
interaction between the ErmC methylase, a member of the family of enzymes
that confer MLS resistance, with its 23S rRNA substrate; and (2) a study of
the interaction between the pEl94 Cop protein and its putative binding site
in plasmid DNA, a reaction that is proposed to regulate the expression of
erythromycin resistance by controlling plasmid copy number.  In the first
case, we shall attempt to distinguish between structural aspects of the
methylase amino acid sequence that are responsible for the ability to
recognize the 23S rRNA substrate and distinguish it from other potential
substrates such as 16S rRNA as well as to identify the parts of the
sequence that are responsible for catalytic (i.e., methylase) activity.  In
the second case, we shall study the interaction between a recently
identified Cop protein specified by plasmid pEl94 and its presumed target
plasmid pEl94 DNA - asking specifically, where does Cop protein bind and
how does this binding ultimately contribute to control the concentration of
plasmid DNA?

## Key facts

- **NIH application ID:** 3127808
- **Project number:** 5R01AI018283-12
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **SAM.gov UEI:** LCLSJAGTNZQ7
- **Principal Investigator:** Bernard Weisblum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $116,533
- **Award type:** 5
- **Project period:** 1981-08-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127808

## Citation

> US National Institutes of Health, RePORTER application 3127808, INDUCIBLE ANTIBIOTIC RESISTANCE (5R01AI018283-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127808. Licensed CC0.

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